Distinct destructive signal pathways of neuronal death in Alzheimer's disease.

Abundant neuron loss is a major feature of Alzheimer's disease (AD). Hypotheses for this loss include abnormal amyloid precursor protein processing (i.e. excess Abeta production, protein aggregation or misfolding), oxidative stress, excitotoxicity and inflammation. Neuron loss is a major cause of dementia in AD; however, it seems that there is no definitive pathway that causes cell death in the AD brain. Here, we examine the hypotheses for neuron loss in AD and pose the argument that the means by which neurons degenerate is irrelevant for cognitive decline. The best treatment for cognitive decline is to prevent the toxicity that first sets the neuron on its path to destruction, which is the production of Abeta peptide.